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1.
AimsCannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7 day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation.Main methodsA murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur.Key findingsOsteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7 days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures.SignificanceThese findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.  相似文献   

2.
A galactomannoglucan (GMG) with an estimated weight-average molar mass of 1.5 × 105 was obtained from an aqueous extract of the mesocarp of fruits of Arecastrum romanzoffianum (Cham.) Becc. by fractionation by Sephacryl S-300 HR and Sephadex G-25. Chemical and spectroscopic studies indicated that GMG has a chain of (1  4)-linked β-d-mannopyranosyl residues, a chain of (1  3)-linked β-d-galactopyranosyl residues, a chain of (1  4)-linked α-d-glucopyranosyl residues, repeating units of β-d-galactopyranosyl-(1  4)-β-d-mannopyranosyl and β-d-mannopyranosyl-(1  4)-α-d-glucopyranosyl and terminal residues of d-galactopyranosyl and d-glucopyranosyl which comprised galactose, mannose and glucose in the molar ratio of 10:37:53. The polysaccharide exhibited significant antiinflammatory activity against carrageenan-induced mouse paw oedema.  相似文献   

3.
Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague–Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p < 0.05). The fasting blood glucose level of CO treated diabetic group was significantly lower than the diabetic group (p < 0.05). Diabetic and CO treated diabetic groups showed a significant increase in the percentage of spleen CD3+ CD4+ T lymphocytes (p < 0.05) when compared with the normal group. However, there was no significant difference in the percentage of spleen CD3+ CD8+ T lymphocytes among all experimental groups. The finding suggested that an aqueous extract of CO leaves has the ability to reduce blood glucose levels in diabetic rats.  相似文献   

4.
The possible role for DNA repair deficiencies in cancer development, namely in breast cancer has been the subject of increasing interest since it has been reported that breast cancer patients might be deficient in the repair of DNA damage. Exposure to ionizing radiation has been pointed out as a risk factor for breast cancer, and the type of DNA lesions induced by this carcinogen can be repaired by homologous recombination DNA repair (HRR) pathway. To evaluate the potential modifying role of some single nucleotide polymorphisms (SNP) in HRR involved genes on the individual susceptibility to breast cancer we carried out a hospital based case–control study in a Caucasian Portuguese population (289 histological confirmed breast cancer patients and 548 control individuals). We genotyped 4 SNPs in 4 different HRR pathway genes, XRCC2 (Ex3 + 442G > A, R188H, rs3218536), XRCC3 (Ex8-5C > T, T241M, rs861539), NBS1 (Ex5-32C > G, E185Q, rs1805794) and RAD51 5′UTR (Ex1-59G > T, rs1801321), tagging 41 SNPs in these genes. The frequency of the different polymorphisms in the Portuguese control population is similar to the ones reported for other Caucasian populations, and the deviation of the Hardy–Weinberg equilibrium was only observed for the XRCC2 (Ex3 + 442G > A, R188H, rs3218536) polymorphism in the control population. The results obtained, after logistic regression analysis, did not reveal a major role of these polymorphisms on breast cancer susceptibility. However, when the population was stratified according to breast feeding (women that breast fed and women that never breast fed) it is observed, in women that never breast fed, that the heterozygous individuals for the XRCC2 (Ex3 + 442G > A, R188H, rs3218536) polymorphism have a decreased risk for breast cancer [adjusted OR = 0.45; 95% CI = 0.22–0.92] (P = 0.03). Additionally, after stratification according to menopausal status, our results suggest that post-menopausal women carrying at least one variant allele for the XRCC3 (Ex8-5C > T, T241M, rs861539) polymorphism have a lower risk for breast cancer [adjusted OR = 0.67; 95% CI, 0.47–0.94] (P = 0.03). Most of the studies suggest that breastfeeding may be responsible for 2/3 of the estimate reduction of breast cancer. The longer the duration of breastfeeding the lower the potential risk associated with breast cancer. Therefore, in our study the potential protective role of the variant allele of XRCC2 (Ex3 + 442G > A, R188H, rs3218536), in never breast fed women, might be related with a more efficient DNA repair activity.  相似文献   

5.
Growing exclusively on stout camphor trees in Taiwan, Antrodia cinnamomea is known for its extraordinary antioxidant and antitumor activities. As an alternative to the limited supply of natural source, cultured A. cinnamomea from solid state or submerged liquid fermentation still offers many of its medicinal effects. To further enhance the production of functional compounds and corresponding activities, oat, wheat, buckwheat and pearl barley were used as substrates for solid state fermentation of A. cinnamomea in this study. Among these cereal-based culturing, the methanol extract of A. cinnamomea mycelia grown on oats showed stronger overall antioxidant properties. EC50 for the antioxidant activity (conjugated diene method), the DPPH radicals scavenging ability and reducing power were estimated to be around 0.57 mg/mL, 1.07 mg/mL and 0.31 mg/mL, respectively. Incubating cultured cells with 150 ppm of the oat-cultured mycelial extract for 24 h greatly reduced the viability of MCF-7 breast cancer cells and HepG2 hepatocellular carcinoma cells to 29% and 76%, while 3T3 normal fibroblasts were virtually unaffected. In general, cereal-based solid state fermentation of A. cinnamomea produced more of the secondary metabolites and their methanolic extracts showed stronger antioxidant and anti-tumor activities than extracts obtained from liquid fermentation at the same concentration.  相似文献   

6.
Green tea (Camellia sinensis, CS), a kind of Chinese tea commonly consumed as a healthy beverage, has been demonstrated to have various biological activities, including antioxidation, antiobesity and anticancer. Our study aims to investigate the antitumor, antimetastasis and antiosteolytic effects of CS aqueous extract both in vitro and in vivo using metastasis-specific mouse mammary carcinoma 4T1 cells. Our results showed that treatment of 4T1 cells with CS aqueous extract resulted in significant inhibition of 4T1 cell proliferation. CS extract induced 4T1 apoptosis in a dose-dependent manner as assessed by annexin-V and propidium iodide staining and caspase-3 activity. Western blot analysis showed that CS increased the expression of Bax-to-Bcl-2 ratio and activated caspase-8 and caspase-3 to induce apoptosis. CS also inhibited 4T1 cell migration and invasion at 0.06–0.125 mg/ml. In addition, CS extract (0.6 g/kg, orally fed daily for 4 weeks) was effective in decreasing the tumor weight by 34.8% in female BALB/c mice against water treatment control (100%). Apart from the antitumor effect, CS extract significantly decreased lung and liver metastasis in BALB/c mice bearing 4T1 tumors by 54.5% and 72.6%, respectively. Furthermore, micro-computed tomography and in vitro osteoclast staining analysis suggested that CS extract was effective in bone protection against breast cancer-induced bone destruction. In conclusion, the present study demonstrated that the CS aqueous extract, which closely mimics green tea beverage, has potent antitumor and antimetastasis effects in breast cancer and could protect the bone from breast cancer-induced bone destruction.  相似文献   

7.
A new series of 3-substituted-4-hydroxycoumarin derivatives was designed, synthesized, and evaluated for CDK inhibiting and anticancer activities. All the synthesized target compounds showed remarkably high affinity and selectivity towards CDK1B, compared to flavopiridol, with Ki values in the low nanomolar range (Ki = 0.35–0.88 nM). Most of them elicited considerable inhibiting effect against CDK9T1 (Ki = 3.26–23.45 nM). Moreover, all the target compounds were tested in vitro against eighteen types of human tumor cell lines. The hydrazone 3a, N-phenylpyrazoline derivative 6b and 2-aminopyridyl-3-carbonitrile derivative 8c were the most potent anticancer agents against MCF-7 breast cancer cell line (IC50 = 0.21, 0.21 and 0.23 nM, respectively). The target compounds 3a, 6b and 8c were further evaluated in MCF-7 breast cancer mouse xenograft model and showed in vivo efficacy at 10 mg/kg dose. The docking study confirmed a unique binding mode in the active site of CDK1B with better score than flavopiridol. Quantitative structure activity relationship study was done and revealed a highly predictive power R2 of 0.81.  相似文献   

8.
A galactoglucomannan (GGM) with an estimated weight-average molar mass of 3.5 × 105 was obtained from an aqueous extract of the mesocarp of fruits of Acrocomia aculeata (Jacq.) Lodd. by fractionation by Sephacryl S-300 HR and Sephadex G-25. Chemical and spectroscopic studies indicated that GGM has a main chain of (1  4)-linked β-d-mannopyranosyl residues attached to an initial chain of (1  3)-linked β-d-galactopyranosyl residues and a terminal chain of (1  4)-linked α-d-glucopyranosyl residues which comprised galactose, glucose and mannose in the molar ratio of 18:22:60. The adjuvant potential of the polysaccharide on the cellular immune response against ovalbumin antigen was investigated using in vivo assays.  相似文献   

9.
In a previous study, the methanolic extract as well as the chloroform fraction of the aerial parts of Caralluma quadrangula (Forssk.) N.E.Br. indigenous to Saudi Arabia showed significant in vitro cytotoxic activity against breast cancer (MCF7) cell line. In a biologically-guided fractionation approach, four acylated pregnane glycosides were isolated from the chloroform fraction of C. quadrangula. The structures of the isolated compounds were elucidated by the analysis of their MS and NMR data. The compounds were identified as 12,20-di-O-benzoylboucerin 3-O-β-d-digitoxopyranosyl-(1  4)-β-d-canaropyranosyl-(1  4)-β-d-cymaropyranoside (1), 12,20-di-O-benzoylboucerin 3-O-β-d-cymaropyranosyl-(1  4)-β-d-canaropyranosyl-(1  4)-β-d-cymaropyranoside (2), 12,20-di-O-benzoylboucerin 3-O-β-d-glucopyranosyl-(1  4)-β-d-digitoxopyranosyl-(1  4)-β-d-canaropyranosyl-(1  4)-β-d-cymaropyranoside (3) and 12,20-di-O-benzoyl-3β,5α,12β,14β,20-pentahydroxy-(20R)-pregn-6-ene 3-O-β-d-glucopyranosyl-(1  4)-β-d-digitoxopyranosyl-(1  4)-β-d-canaropyranosyl-(1  4)-β-d-cymaropyranoside (4). The isolated compounds were tested for their cytotoxic activity against breast cancer (MCF7) cell line.  相似文献   

10.
Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids, directly from a crude extract of Ipomoea muricata. The experiment was performed with a two-phase solvent system composed of methyl tert-butyl ether (MtBE)–acetonitrile–water (4:1:5, v/v) where triethylamine (10 mM) was added to the upper organic stationary phase as a retainer and trifluoroacetic acid (10 mM) to the aqueous mobile phase as an eluter. From 4 g of crude extract, 210 mg lysergol and 182 mg chanoclavine were obtained in 97% and 79.6% purities. Total yield recovery was >95%. Isolated alkaloids were characterized on the basis of their 1H, 13C NMR and ESI-MS data.  相似文献   

11.
Several novel series of C75 derivatives were synthesized and evaluated for their FAS inhibitory activities. The results showed compound 4-methylene-2-octyl-5-oxo-tetrahydro-thiophene-3-carboxylic acid (1c) had more effective FAS inhibitory (IC50 was 2.56 μM and T.I. was 9.26) and potent anti-tumor activities on HL60 and Hela cells in vitro (IC50 were 5.38 μM and 46.10 μM, respectively).  相似文献   

12.
《Microbiological research》2014,169(4):294-300
The effectiveness of aqueous extracts of various medicinal plants in detoxification of aflatoxin B1 (AFB1) was tested in vitro by thin-layer chromatography and enzyme-linked immunosorbent assay (ELISA). Among the different plant extracts, the leaf extract of Vasaka (Adhatoda vasica Nees) showed the maximum degradation of AFB1 (≥98%) after incubation for 24 h at 37 °C. The aflatoxin detoxifying activity of the A. vasica leaf extract was significantly reduced by heating to 100 °C for 10 min or autoclaving at 121 °C for 20 min. Dialysis had no effect on aflatoxin detoxifying ability of A. vasica extract and the dialyzed extract showed similar level of detoxification of AFB1 as that of the untreated extract. A time course study of aflatoxin detoxification by A. vasica extract showed that 69% of the toxin was degraded within 6 h and ≥95% degradation was observed after 24 h of incubation. Detoxification of AFB1 by A. vasica extract was further confirmed by liquid chromatography–mass spectrometry (LC–MS) analysis. Phytochemical analysis revealed the presence of alkaloids in methanolic extract of A. vasica leaves. A partially purified alkaloid from A. vasica leaves by preparative TLC exhibited strong AFB1 detoxification activity.  相似文献   

13.
BackgroundTransportation of anticancer drugs such as anthracyclines across the membrane is regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 (ABCB1). Polymorphisms in the ABCB1 gene (1236C > T, 2677G > T/A, 3435C > T) have been found to be associated with intrinsic and acquired cross resistance to these anticancer drugs. Therefore, the aim of this study is to evaluate the influence of ABCB1 gene polymorphisms in breast cancer treatment outcomes in terms of response and toxicity.MethodResponse to neo-adjuvant chemotherapy was evaluated in 100 patients while grade 2–4 toxicity was followed in 207 patients, who had undergone FEC/FAC chemotherapy. Genotyping for ABCB1 polymorphisms was done by PCR-RFLP. Chi square and logistic regression analyses were used to calculate Odd's ratio using SPSS ver 17.0. A meta analysis was also performed using Comprehensive Meta Analysis Ver 2.ResultsIn response evaluation, 1236C > T polymorphism was significantly associated with treatment response for CT genotype [OR = 5.17(1.3–20.2), P = 0.018] and in dominant model (CC vs CT + TT) [OR = 4.63(1.25–17.0), P = 0.021]. In the toxicity group, the T allele of 1236C>T was associated with grade 2–4 tocxicity [OR 1.48(1.00–2.20), P = 0.049] and the association was also significant in the recessive model [OR 1.88(1.05–3.39), P = 0.033]. For other two SNPs 2677G>T/A and 3435C>T no association was seen with either treatment response or grade 2–4 toxicity. In meta analysis, no overall association was found.ConclusionIn our study, significant association was seen for ABCB1 1236C>T polymorphism with treatment response. The meta analysis did not show overall association with treatment outcomes.  相似文献   

14.
Bioassay-guided fractionation of the EtOAc extract of the root of Erythrina addisoniae (Leguminosae) resulted in the isolation of four new (14), along with 2 known prenylated isoflavonoids (56). The structures of the isolates were assigned on the basis of spectroscopic data analysis, focusing on interpretation of 1D and 2D NMR, and MS data. All the isolates were evaluated for their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), as well as their growth inhibition on MCF7, adriamycin-resistant MCF7 (MCF7/ADR), and MDA-MB-231 breast cancer cell lines. Compounds which exhibited PTP1B inhibitory activity (IC50 values ranging from 4.6 ± 0.3 to 24.2 ± 2.1 μM) showed potential cytotoxic activity (IC50 values ranging from 3.97 ± 0.17 to 11.4 ± 1.9 μM). Taken together, our data suggest that prenylated isoflavonoids, especially the isoflavone-type skeleton could be considered as new lead compounds against breast cancer via PTP1B inhibition.  相似文献   

15.
IntroductionThe objective assessment of therapeutic response is a major diagnostic and therapeutic management in breast cancer with bone metastases. The objective of the study was to test performance of an automated method for quantifying the extent of skeletal tumour involvement in breast cancer, using the Bone Scan Index (BSI), and study if BSI could be considered as an imaging biomarker of metastatic bone disease.Materials and methodsOne hundred and two planar bone scans, corresponding to 34 treatment (three successive bone scans) of 31 patients were retrospectively analyzed. Each image was reviewed by two nuclear physicians, a senior and a junior. Exini Bone® software calculated automatically the BSI for each scan.ResultsAt 3 times of the study, agreements between automatic and visual methods were intermediate: 55.88% (kappa = 0.3704), 52.94% (kappa = 0.3052) and 52.94% (kappa = 0.2173) with junior nuclear physician and 52.94% (kappa = 0.33), 55.88% (kappa = 0.3333) and 50% (kappa = 0.1939) with senior nuclear physician. Six initial bone scans (17%) were considered normal (BSI = 0) by the software; with bone lesions confirmed by morphological imaging and/or histology. Agreements between junior and senior were high, with kappa = 0.81, 0.91 and 0.94 at 3 times of the study. Confrontation with routine analysis showed significant variability with agreements from 47.06 to 76.47%. We did not find any significant relationship between evolution of BSI and tumor markers over time. Only a trend between evolution of CA15-3 and BSI was observed. We did not find any significant association between overall survival and value of BSI.ConclusionIn breast cancer, the fully automated platform of quantifying the BSI seems to have limitations, because of characteristics of bone metastases of breast cancer, and their scintigraphic translation. BSI seems to be an interesting tool, and it could be improved: development of diagnostic “assisted” by computer, combining power of medical knowledge and technical computing could help to score bone disease, and allow standardized monitoring.  相似文献   

16.
To investigate the anti-cancer properties of soil-borne actinobacteria, MJM 8637, the glutathione S-transferase pi (GST-pi) assay, anti-tumor necrosis factor (TNF)-α assay, the level of antioxidant potential by DPPH radical scavenging activity, NO scavenging activity, and ABTS radical scavenging activity in ethyl acetate extract were determined. The 16S rDNA sequencing analysis revealed that Streptomyces sp. strain MJM 8637, which was isolated from Hambak Mountain, Korea, has 99.5% similarity to Streptomyces atratus strain NBRC 3897. The physiological and the morphological characteristics of the strain MJM 8637 were also identified. The ethyl acetate extract of MJM 8637 inhibited TNF-α production approximately 61.8% at concentration 100 μg/ml. The IC50 value of the strain MJM 8637 extract on GST-pi was identified to be 120.2 ± 1.6 μg/ml. In DPPH, NO, and ABTS radical scavenging assays, the IC50 values of the strain MJM 8637 extract were found to be 977.2 μg/ml, 1143.7 μg/ml, and 454.4 μg/ml, respectively. The ethyl acetate extract of the strain MJM 8637 showed 97.2 ± 1.3% of cell viability at 100 μg/ml in RAW 264.7 cell viability assay. The results obtained from this study suggest that the ethyl acetate extract of Streptomyces sp. strain MJM 8637 could be considered as a potential source of drug for the cancers that have multidrug resistance with its GST-pi inhibition and anti-inflammation activities, and low cytotoxicity.  相似文献   

17.
The coupling of the intervertebral disc (IVD) and vertebra as a biomechanical unit suggests that changes in the distribution of pressure within the IVD (intradiscal pressure, IDP) as a result of disc degeneration can influence the distribution of bone density within the vertebra, and vice versa. The goal of this study was to assess the correspondence between IDP and bone density in the adjacent vertebrae, with emphasis on how this correspondence differs between healthy and degenerated IVDs. Bone density of the endplates and subchondral bone in regions adjacent to the anterior and posterior annulus fibrosus (aAF and pAF, respectively) and nucleus pulposus (NP) was measured via quantitative computed tomography (QCT) in 61 spine segments (T7-9, T9-11, T10-12; 71 ± 14 years). IDP was measured in the aAF, NP, and pAF regions in 26 of the spine segments (68 ± 16 years) while they were tested in flexed (5°) or erect postures. Disc degeneration was assessed by multiple grading schemes. No correlation was found between bone density and IDP in either posture (p > 0.104). Regional variations in IDP and, to a greater extent bone density, were found to change with advancing degeneration: both IDP (p = 0.045) and bone density (p = 0.024) decreased in the NP region relative to the aAF region. The finding of only a modest correspondence between degeneration-associated changes in IDP and bone density may arise from complexity in how IDP relates to mechanical force transmission through the endplate and from limitations of the available IVD grading schemes in estimating the mechanical behavior of the IVD.  相似文献   

18.
A series of 4-(amido-biarylether)-quinolines was prepared as potential LXR agonists. Appropriate substitution with amide groups provided high affinity LXR ligands, some with excellent potency and efficacy in functional assays of LXR activity. Novel amide 4g had a binding IC50 = 1.9 nM for LXRβ and EC50 = 34 nM (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide substitution are potent LXR agonists  相似文献   

19.
The occurrence of intestinal parasites of Columba livia domestica has been on the increase, leading to high economic and production losses with more fatal cases. This study was designed to investigate the prevalence of cestodes in pigeons and determine the efficacy of Typha angustata extract and sulphadimidine against these cestodes in the domestic pigeon. A total of 30 pigeons were examined. 18 (60%) pigeons were found infected with only one type of cestode species (Raillietina spp.). The difference in prevalence between males and females was statistically significant (χ2 = 8.167, p = 0.004). The mean EPG count in group A (treated with T. angustata extract) before treatment and after treatment was 176 ± 4.33 and 155 ± 4.24, respectively. In group B (treated with sulphadimidine), the mean EPG calculated before treatment and after treatment was 184 ± 6.74 and 35 ± 3.53, respectively. The efficacy at day 28 of T. angustata and Sulphadimidine was 11.93% and 80.97%, respectively. It was concluded on the basis of the EPG and efficacy data that T. angustata extract had low efficacy against raillietiniasis, while as sulphadimidine, which is also used before to treat different intestinal parasites, had a good efficacy against raillietiniasis. Further studies are required to know the prevalence of other gastrointestinal parasites in pigeons and efficacy of different medicinal plants against such parasites.  相似文献   

20.
FDG-PET is useful for metabolic analysis of metastatic cells. Based on a retrospective study relating to 20 cases of osseous metastases (MO), and a literature review, we will try to specify the main characteristics of bone metastases detected with FDG-PET. In our study, the primary malignant findings included lymphoma (n = 7), lung cancer (n = 5), breast cancer (n = 4), colon cancer (n = 2), melanoma (n = 1), and nasopharyngeal cancer (n = 1). On FDG-PET, 4 patients had a solitary metastatic focus (20%), 1 patient had two metastatic focuses (5%) and 15 patients had multiple lesions (75%). Most of the lesions showed intense abnormal uptake with SUVmax > 4.0 (14 patients, 70%); 6 patients had both intense and moderate FDG uptake with SUVmax > 2.1. Only 6 patients had MO diagnosed with standard diagnostic procedures (SDP) before FDG-PET. However, FDG-PET consistently revealed more metastatic foci missed by SDP. We conclude that FDG-PET is better than SDP in detecting all bone metastases at all sites of the skeleton according to the data of the literature.  相似文献   

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